Maternal Western diet causes inflammation, hair loss in newborn mice

Female mice that ate a Western diet produced toxic milk that triggered inflammation in their newborns, causing many of them to lose their fur, UT Southwestern Medical Center researchers report in the journal Genes & Development.

These findings are intriguing in light of research that suggests inflammation may increase the incidence of diabetes and coronary artery disease, said Yihong Wan, PhD, senior author of the study in the journal’s June 15 issue and an Assistant Professor of Pharmacology at UT Southwestern.

“Because Western diet consumption is associated with the current epidemic of metabolic diseases such as obesity and diabetes, as well as heart attack(in humans), we decided to investigate the consequences of such a diet on newborn mice,” she said.

Milk quality impacts the health of newborns and might influence their development of chronic diseases in adulthood. Earlier studies of diet and breast milk in mice often measured newborn weight gain and rarely looked at inflammation, she said.

The researchers also found two ways to protect the mice from fur loss by manipulating their immune systems, she said.

In standard rodent chow, fat comprises 12 percent of total calories. By comparison, rodent chow patterned on the diet common in Western countries gets 40 percent of total calories from fat and is also higher in cholesterol and sugar than standard chow.

Breast milk from mice that consume regular chow is rich in short- and medium-chain fatty acids. In contrast, Western-diet chow causes production of milk with high levels of long-chain and saturated fatty acids, triggering inflammation in the newborn and fur loss in about 70 percent of them, Dr. Wan said. The most obvious signs of inflammation – hair loss and skin swelling – went away after weaning, she added.

Earlier studies had indicated that saturated fatty acids induce inflammation via the Toll-like receptors (TLRs), key components of the innate immune system that launches the body’s first response to infection. Because of those studies, the researchers decided to see if the TLRs played a role in the diet-induced inflammation.

“We found the inflammation in the newborn mice functioned through the Toll-like receptors,” Dr. Wan said. “When we tested mice genetically lacking in those receptors, resulting in a reduced immune response, they showed no loss of fur and far fewer signs of inflammation when drinking the pro-inflammatory milk,” she said.

That finding made the researchers wonder if they could find a way to prevent inflammation in Western-diet nursed newborns with intact immune systems. Dr. Wan and her colleagues showed that providing a chemical that kept the TLRs from working protected the newborns from fur loss – a sign of inflammation in mice – when they consumed the Western-diet milk, Dr. Wan said.

“We conclude that Western-diet feeding causes mice to produce inflammatory breast milk that contains excessive long-chain fatty acids and is toxic to the newborn. Although the results in mice cannot be directly applied to humans, this line of research could represent a new way to understand the roots of metabolic and inflammatory diseases,” Dr. Wan said.

Other UT Southwestern researchers involved in the study include lead author and postdoctoral researcher Yang Du, PhD; Marie Yang, PhD, a former postdoctoral researcher now at the University of Liverpool, United Kingdom; Syann Lee, PhD, an instructor of internal medicine; Cassie Behrendt, a research assistant of immunology; and Lora Hooper, PhD, Associate Professor of Immunology and a Howard Hughes Medical Institute investigator. Alan Saghatelian, PhD, an Associate Professor of Chemistry at Harvard University, also contributed to the study.